UA & Body Fluids 7.2 (Harr)

Which of the following dyes are used in Sternheimer-Malbin stain?

Crystal violet and safranin

Sternheimer-Malbin stain is a supravital stain used to help differentiate renal tubular epithelium from transitional cells and PMNs. The mononuclear cells are clearly distinguished from both live and dead PMNs. Transitional cells have pale blue cytoplasm, but renal cells take up both dyes, resulting in an azurophilic appearance (orange-purple cytoplasm and dark purple nucleus).

Which of the following statements regarding WBCs in urinary sediment is true?

WBC casts indicate that pyuria is of renal, rather than lower urinary, origin

The majority of WBCs in the urinary sediment will be PMNs. Eosinophils and mononuclear WBCs will occasionally be seen. High numbers of eosinophils often indicate an allergic drug reaction, causing inflammation in the medullary interstitium and tubules. Mononuclear cells are especially likely in patients with chronic inflammatory diseases and in renal transplant rejection, where they may account for as many as 30% of the WBCs. Glitter cells are PMNs with highly refractile granules exhibiting Brownian movement. They are seen only when urine SG is below 1.020. These cells resist staining with Sternheimer-Malbin stain and are considered to be living (fresh) WBCs. When seen in large numbers, they indicate urinary tract injury (with pseudopod extensions, they point to infection). The presence of bacteria in urine in the absence of PMNs usually results from contamination by vaginal or skin flora that multiply in vitro, especially in unrefrigerated specimens. The presence of WBC casts is always significant, and when associated with pyuria and bacteriuria, indicates renal involvement in the infection.

Which description of sediment with Sternheimer-Malbin stain is correct?

Transitional epithelium: cytoplasm pale blue,nucleus dark blue

After staining with Sternheimer-Malbin stain, transitional epithelium are readily differentiated from renal tubular cells and WBCs because their cytoplasm is pale blue. Live WBCs exclude Sternheimer-Malbin stain, while dead cells stain with a deeply blue-purple nucleus and pale orange-blue cytoplasm. Renal epithelium have an orange-purple cytoplasm and dark purple nucleus. Squamous epithelium have a blue or purple cytoplasm and an orange-purple nucleus. Red cells stain very pale pink or not at all and hyaline casts stain faintly pink.

SITUATION: A 5-mL urine specimen is submitted for routine urinalysis and analyzed immediately. e SG of the sample is 1.012 and the pH is 6.5. The dry reagent strip test for blood is a large positive (3+) and the microscopic examination shows 11-20 RBCs per HPF. e leukocyte esterase reaction is a small positive (1+), and the microscopic examination shows 0-5 WBCs per HPF. What is the most likely cause of these results?

Insufficient volume is causing microscopic results to be underestimated

Given the SG and pH, most RBCs and WBCs will be intact. Both the RBC and WBC counts are lower than expected from the dry reagent strip results. Myoglobin or free hemoglobin may account for the poor correlation between the blood reaction and the RBC count, but this does not explain the lower than expected WBC count. Microscopic reference ranges are based upon concentrating a uniform volume of sediment from 12 mL of urine. When less urine is used, falsely low results will be obtained unless corrective action is taken. The specimen should be diluted with normal saline to 12 mL, then centrifuged at 450 × g for 5 minutes. Sediment should be prepared according to the established procedure and the results multiplied by the dilution factor (in this case, 12 ÷ 5, or 2.4).

Which of the following statements regarding epithelial cells in the urinary system is correct?

Transitional cells originate from the upper urethra, ureters, bladder, or renal pelvis

Caudate cells are transitional epithelium that have a sawtooth-shaped tail and are found in the urinary bladder and the pelvis of the kidney. Transitional epithelia line the upper two-thirds of the urethra and the ureters as well as the urinary bladder and renal pelvis. Renal tubular cells may be columnar, polyhedral, or oval, depending upon the portion of the tubule from which they originate. Cells from the proximal tubule are columnar and have a distinctive brush border. Squamous epithelia line the vagina and lower third of the urethra.

Which of the statements regarding examination of unstained sediment is true?

Large numbers of transitional cells are often seen after catheterization

Renal cells and PMNs are about the same size and can be confused in unstained sediment. Catheterization often releases large clumps or sheets of transitional and squamous cells. These should be distinguished from neoplastic cells derived from the urinary bladder. When cells appear atypical (e.g., large cells in metaphase), they should be referred to a pathologist for cytological examination. Nonbudding yeast cells are approximately the same in size and appearance as RBCs. When RBCs are seen in the absence of a positive blood test, the probability of an error in microscopy is high. The microscopic examination should be reviewed for the presence of yeast.

Which of the following statements regarding cells found in urinary sediment is true?

Renal tubular cells are often polyhedral and have an eccentric round nucleus

Transitional epithelial cells readily take up H2O and appear much larger than renal cells or WBCs when urine is hypotonic. Transitional cells are considered a normal component of the sediment unless present in large numbers and associated with signs of inflammation such as mucus and PMNs, or presenting features of malignant cells. In contrast, renal cells are significant when seen conclusively in the sediment. They are often teardrop, polyhedral, or elongated cells with a round eccentric nucleus. Conclusive identification requires staining. Trichomonas vaginalis displays an indistinct nucleus and two pairs of prominent anterior flagella. Amorphous urate crystals deposited on the slide may be mistaken for granular or blood casts.

Which of the following statements regarding RBCs in the urinary sediment is true?

RBCs of glomerular origin often appear dysmorphic

RBCs are difficult to distinguish from nonbudding yeast in unstained sediment. RBCs tumble when the cover glass is touched and will lyse when the sediment is reconstituted in normal saline containing 2% v/v acetic acid. A nonhemolyzed trace blood reaction confirms the presence of RBCs. RBCs have a granular appearance in hypertonic urine due to crenation. The RBC membrane becomes distorted when passing through the glomerulus, often appearing scalloped, serrated, or invaginated. Such cells are called dysmorphic RBCs and are associated with glomerulonephritis.

Renal tubular epithelial cells are shed into the urine in largest numbers in which condition?

Cytomegalovirus (CMV) infection of the kidney

Although seen in glomerulonephritis and pyelonephritis, the largest numbers of renal tubular cells appear in urine in association with viral infections of the kidney. Renal epithelium may show characteristic viral inclusions associated with CMV and rubella. High numbers of renal epithelium are also found in the sediment of patients with drug-induced tubular nephrosis and some cases of heavy metal poisoning. Renal tumors do not usually shed cells into the urine.

The ova of which parasite may be found in the urinary sediment?

Schistosoma hematobium

Ova of S. hematobium are most often recovered from urine because the adult trematodes colonize the blood vessels of the urinary bladder. The eggs are approximately 150 × 60 μm and are nonoperculated. They are yellowish and have a prominent terminal spine.

Oval fat bodies are often seen in:

Nephrotic syndrome

Oval fat bodies are degenerated renal tubular epithelia that have reabsorbed cholesterol from the filtrate. Although they can occur in any inflammatory disease of the tubules, they are commonly seen in the nephrotic syndrome, which is characterized by marked proteinuria and hyperlipidemia.

Which statement regarding urinary casts is true?

Many hyaline casts may appear in urinary sediment after jogging or exercise

Proteinuria accompanies cylindruria because protein is the principle component of casts. After strenuous exercise hyaline casts may be present in urinary sediment in significant numbers but will disappear after resting for at least 24 hours . Casts more readily dissolve in alkaline urine. The finding of a single cast even a cellular cast is not indicative of renal disease and should be considered a chance occurance

Which condition promotes the formation of casts in the urine?

Reduced filtrate formation

Cast formation is promoted by an acid filtrate, high solute concentration, slow movement of filtrate, and reduced filtrate formation. The appearance of a cast is dependent upon the location and time spent in the tubule, as well as the chemical and cellular composition of the filtrate.

The mucoprotein that forms the matrix of a hyaline cast is called:

Tamm-Horsfall protein

Hyaline casts are composed of a mucoprotein called Tamm-Horsfall protein. In addition, casts may contain cells, immunoglobulins, light chains, cellular proteins, fat, bacteria, and crystalloids.

"Pseudocasts" are often caused by:

Amorphous urates

Pseudocasts are formed by amorphous urates that may deposit in uniform cylindrical shapes as the sediment settles under the cover glass. They may be mistaken for granular or blood casts. However, they are highly refractile and lack the well-defined borders of true casts.

Which of the following statements regarding urinary casts is correct?

Broad casts are associated with severe renal tubular obstruction

There is no clinical difference between fine and coarse granular casts. Granular casts may form by degeneration of cellular casts, but some show no evidence of cellular origin. Granular casts may form from inclusion of urinary calculi, but some are of unknown etiology. Cylindruria refers to the presence of casts in the urine. Hyaline casts may be seen in small numbers in normal patients and in large numbers following strenuous exercise and long-distance running. Hyaline casts may also be increased in patients taking certain drugs such as diuretics. Broad casts form in dilated or distal tubules and indicate severe tubular obstruction seen in chronic renal failure. Waxy casts form when there is prolonged stasis in the tubules and signal end-stage renal failure. Cylindroids are casts with tails and have no special clinical significance.

A sediment with moderate hematuria and RBC casts most likely results from:

Acute glomerulonephritis

Red-cell casts indicate the renal origin of hematuria. Urinary tract obstruction may be associated with hematuria from ruptured vessels, but not casts. WBCs and WBC casts predominate in pyelonephritis. Sediment in chronic glomerulonephritis is variable, but usually exhibits moderate to severe intermittent hematuria. In addition, pyuria and cylindruria (with granular, blood, broad, waxy, and epithelial casts) are frequent. In nephrotic syndrome, the sediment may be unremarkable except for the presence of oval fat bodies and hyaline casts. In some cases, fatty, waxy, and epithelial cell casts may also be found.

Urine sediment characterized by pyuria with bacterial and WBC casts indicates:

Pyelonephritis

Pyelonephritis results from bacterial infection of the renal pelvis and interstitium. It is characterized by polyuria resulting from failure of the tubules to reabsorb fluid. Obstruction of tubules and compression by WBCs may reduce glomerular filtration as well as H2O reabsorption. The finding of WBC casts helps to differentiate pyelonephritis from urinary tract infection.

Which type of casts signals the presence of chronic renal failure?

Waxy casts

Waxy casts form from the degeneration of cellular casts. Because the casts must remain lodged in the tubule long enough for the granular protein matrix to waxify, they are associated with chronic and end-stage renal failure. Both waxy and broad casts form in chronic renal failure when there is severe stasis, and they are associated with a poor prognosis.

SITUATION: Urinalysis of a sample from a patient suspected of having a transfusion reaction reveals small yellow-brown crystals in the microscopic examination. Dry reagent strip tests are normal with the exception of a positive blood reaction (moderate) and trace positive protein. The pH of the urine is 6.5. What test should be performed to positively identify the crystals?

Prussian blue stain

A positive blood test and trace protein occurring with a normal test for urobilinogen and an absence of RBCs are consistent with an intravascular transfusion reaction. Small yellow-brown granular crystals at an acid pH may be uric acid, bilirubin, or hemosiderin. Bilirubin crystals are ruled out by the negative dry reagent strip test for bilirubin. Potassium ferrocyanide is used in the Prussian blue staining reaction to detect hemosiderin deposits in urinary sediment. Hemosiderin is associated with hemochromatosis and increased RBC destruction. Causes of urinary hemosiderin include transfusion reaction, hemolytic anemia, and pernicious anemia.

When examining urinary sediment, which of the following is considered an abnormal finding?

1 renal cell casts per LPF

Epithelial casts are rarely seen but indicate a disease process affecting the renal tubules. They are associated with diseases causing necrosis of the tubules such as hepatitis, CMV, and other viral infections, and mercury and ethylene glycol toxicity. Even occasional cellular casts are considered clinically significant.

SITUATION: A urine sample with a pH of 6.0 produces an abundance of pink sediment after centrifugation that appears as densely packed yellow- to reddish-brown granules under the microscope. The crystals are so dense that no other formed elements can be evaluated. What is the best course of action?

Suspend the sediment in prewarmed saline,then repeat centrifugation

Urates are yellow- or reddish-brown granules and form in acid or neutral urine. They often form following refrigeration of urine and can be dissolved by addition of warm saline or dilute NaOH. Amorphous phosphates are colorless and form in neutral or alkaline urine. They dissolve in dilute acetic acid but precipitate if heated

How can hexagonal uric acid crystals be distinguished from cystine crystals?

Cystine gives a positive nitroprusside test after reduction with sodium cyanide

Flat six-sided uric acid crystals may be mistaken for cystine crystals. Both crystals form at an acid to neutral pH. Cystine crystals are colorless, while uric acid crystals are pigmented (yellow, reddish brown). Cystine transmits polarized light and is soluble in dilute HCl. Uric acid is insoluble in HCl and is less anisotropic. Cystine is reduced by NaCN forming cysteine. The -SH group of cysteine reacts with nitroprusside to form a red color.

The presence of tyrosine and leucine crystals together in a urine sediment usually indicates:

Chronic liver disease

Tyrosine crystals may occur in tyrosinemia, an inborn error of tyrosine metabolism caused by a deficiency of fumarylacetoacetate hydrolase, p-hydroxyphenylpyruvic acid oxidase, or tyrosine aminotransferase (causes of tyrosinuria). However, when seen along with leucine crystals, the cause is chronic liver disease, usually cirrhosis of the liver. Tyrosine usually forms fine brown or yellow needles, and leucine forms yellow spheres with concentric rings.

Which of the following crystals is considered nonpathological?

Ammonium biurate

Abnormal crystals are those that result from a pathological process. Hemosiderin crystals result from intravascular RBC destruction. Bilirubin crystals are found in severe necrotic and obstructive liver diseases, and cholesterol crystals in nephrotic syndrome, diabetes mellitus, and hypercholesterolemia

At which pH are ammonium biurate crystals usually found in urine?

Alkaline urine only

Ammonium biurate is often called a "thornapple" crystal because it forms a dark brown spiny sphere. Calcium carbonate is another common crystal that is seen only in alkaline urine. Sodium urate and uric acid form in acid or neutral urine.

Which of the following crystals is seen commonly in alkaline and neutral urine?

Magnesium ammonium phosphate

Magnesium ammonium phosphate, also called triple phosphate, may be present in neutral or alkaline urine. Most commonly, triple phosphate crystals are six-sided plates that resemble a coffin lid. Crystals containing phosphates do not occur in acid urine.

Which crystal appears in urine as a long, thin hexagonal plate, and is linked to ingestion of large amounts of benzoic acid?

Hippuric acid. Hippuric acid forms long, colorless, flat six-sided plates. It results from the metabolism of benzoic acid and resembles the "coffin lid" appearance of triple phosphate. It may occur normally as a result of ingestion of vegetables preserved with benzoic acid.

Small yellow needles are seen in the sediment of a urine sample with a pH of 6.0. Which of the following crystals can be ruled out?

Cholesterol crystals

Cholesterol crystals are colorless rectangular plates that often have a notched corner and appear stacked in a stair-step arrangement. Cholesterol crystals are highly anisotropic and can be positively identified using a polarizing microscope. Bilirubin, sulfa, or uric acid crystals may occur as small yellow or yellow-brown needles or rods in neutral or acid urine. Bilirubin crystals should be suspected when the dry reagent strip test for bilirubin is positive and cells in the sediment are dark yellow (bile stained). Sulfa crystals are soluble in acetone, concentrated HCl, and NaOH. They can be confirmed by the lignin test in which one drop of sediment and one drop of 10% HCl react with newsprint to produce a yellow-orange color.

Oval fat bodies are derived from:

Renal tubular epithelium

Oval fat bodies form from degenerated renal epithelial cells that have reabsorbed cholesterol from the filtrate. They stain with Oil Red O or Sudan III. The fat globules within the cells give a Maltese cross effect when examined under polarized light.

Oval fat bodies are often associated with:

Lipoid nephrosis

The term lipoid nephrosis is a synonym for idiopathic (primary) nephrotic syndrome. Like other forms of nephrotic syndrome, it is associated with gross proteinuria, edema, and hyperlipidemia; however, the idiopathic form is also associated with hematuria. It is common in children, and often associated with mutations that affect podocyte structure.

Urine of constant SG ranging from 1.008 to 1.010 most likely indicates:

Renal tubular failure

The SG of the filtrate in Bowman's space is approximately 1.010. Urine produced consistently with a SG of 1.010 has the same osmolality of the plasma and results from failure of the tubules to modify the filtrate.

Which of the following characterizes prerenal failure, and helps to differentiate it from acute renal failure caused by renal disease?

BUN:creatinine ratio of 20:1 or higher

Prerenal failure is caused by deficient renal blood flow. The tubules are undamaged and will reabsorb more BUN than normal because filtrate flow is slow. Under the influence of aldosterone, they reabsorb sodium and concentrate the urine. The BUN:creatinine ratio and U:P osmolal ratio are very high and sodium output low. In renal disease, the BUN:creatinine ratio is 10 or less, the U:P osmolal ratio approaches 1.0, and the daily sodium excretion is high.

Which of the following conditions characterizes chronic glomerulonephritis and helps to differentiate it from acute glomerulonephritis?

Polyuria

Acute glomerulonephritis results in severe compression of the glomerular vessels. This reduces filtration, causing a progression from oliguria to anuria. In contrast, polyuria is associated with chronic glomerulonephritis, which causes scarring of the collecting tubules. Both acute and chronic glomerulonephritis cause low urine osmolality, azotemia, acidosis, hypertension, proteinuria, and hematuria.

Which of the following conditions is seen in acute renal failure and helps to differentiate it from prerenal failure?

Abnormal urinary sediment

Reduced glomerular filtration as evidenced by low creatinine clearance characterizes both prerenal and acute renal failure. This results in retention of fluid, causing edema, reduced urine volume, hypertension, uremia, and hyperkalemia in both prerenal and acute renal failure. The kidneys are not damaged in prerenal failure and, therefore, the microscopic examination is usually normal.

Which of the following conditions characterizes acute renal failure and helps to differentiate it from chronic renal failure?

Hyperkalemia

In acute renal failure, reduced glomerular filtration coupled with decreased tubular secretion results in hyperkalemia. In chronic renal failure, scarring of the collecting tubules prevents salt and H2O reabsorption. This can result in normal or low serum potassium despite reduced glomerular filtration. The sediment in chronic renal failure is characterized by intermittent heavy hematuria and proteinuria.

The serum concentration of which analyte is likely to be decreased in untreated cases of acute renal failure?

Calcium

Decreased glomerular filtration in renal failure results in high serum creatinine, BUN, and uric acid. Failure of the tubules results in retention of hydrogen ions and phosphates, causing acidosis and an increased anion gap. The tubules fail to respond to parathyroid hormone, resulting in excessive loss of calcium in urine. Serum sodium is usually normal or slightly increased, while hyperkalemia is a constant finding in acute renal failure.

Which of the following conditions is associated with the greatest proteinuria?

Nephrotic syndrome

Although all four conditions are associated with proteinuria, it is greatest in the nephrotic syndrome. Urinary albumin loss is typically in excess of 4 g/day or 3 mg per mg creatinine, causing dry reagent strip protein tests to give 3+ to 4+ reactions. In contrast to glomerulonephritis and pyelonephritis, the urinary sediment in nephrotic syndrome in adults is not usually characterized by either hematuria or pyuria. Various casts, lipid laden renal epithelial cells, and oval fat bodies are usually found.

Which of the following conditions is often a cause of glomerulonephritis?

Systemic lupus erythematosus

Autoimmune diseases, diabetes mellitus, and nephrotoxic drugs are common causes of acute glomerulonephritis. Autoimmune damage may result from the deposition of antigen-antibody complexes and complement-mediated damage such as occurs in poststreptococcal glomerulonephritis, or from the production of autoantibodies that attack the basement membrane as in Goodpasture's syndrome. Acute glomerulonephritis is often classified by the pattern of injury rather than the cause. For example, insulin deficiency produces sclerotic vascular damage to the glomeruli, often resulting in crescentic glomerulonephritis. Group A strep and SLE result in immunologically mediated damage to the glomeruli usually causing membranous or membranoproliferative glomerulonephritis. Cytomegalovirus infections and heavy metal poisoning cause damage to the tubules, resulting in nephrosis.

Acute pyelonephritis is commonly caused by:

Bacterial infection of medullary interstitium

Acute pyelonephritis is caused by infection of the medullary interstitium, usually by coliforms that enter from the lower urinary tract. Escherichia coli is the most commonly implicated bacterium. Since it is focused in the medulla, the disease involves mainly the tubules. As opposed to acute glomerulonephritis, pyelonephritis is not associated with reduced creatinine clearance, azotemia, or oliguria. Reabsorption of salt and water are blocked, resulting in hyperkalemia, acidosis, and polyuria.

Which of the following is associated with nephrotic syndrome?

Hyperlipidemia

Although casts may be present, the urinary sediment in nephrotic syndrome is not characterized by RBCs and WBCs or RBC, blood, and WBC casts. In nephrotic syndrome unlike renal failure (nephritic syndrome), the creatinine clearance and serum potassium are usually normal. Nephrotic syndrome can be secondary to other renal disease, infections, and drug treatments. In such cases, it is often transient. When it follows the anuric phase of acute glomerulonephritis, it signals a reversal in the course of the disease.

Which of the following conditions is a characteristic finding in patients with obstructive renal disease?

Azotemia

Obstructive renal disease may result from renal or urinary tract calculi, benign prostatic hypertrophy, chronic urinary tract infection, or urogenital malignancy. Obstruction causes the hydrostatic pressure in Bowman's space to increase. This pressure opposes glomerular filtration. If the hydrostatic pressure in Bowman's space equals the hydrostatic pressure in the glomeruli, then filtrate will not be produced, resulting in anuria. Postrenal failure produces many of the same serum abnormalities as acute renal failure, including hyperkalemia, acidosis, edema, and azotemia. The urinary sediment will often be abnormal, as well. Bacteriuria and pyuria are common, and hematuria may result from rupture of the vasa recta or other blood vessels.

Whewellite and weddellite kidney stones are composed of:

Calcium oxalate

Over three-fourths of urinary tract stones are composed of calcium salts, and hyperparathyroidism is commonly associated with calcium stones. Stones composed of magnesium ammonium phosphate are called struvite and lodge in the renal pelvis, causing a characteristic "staghorn" appearance on radiographic examination. Stones mainly composed of calcium phosphate are called hydroxyapatite or bushite, depending upon the calcium composition. Stones of CaCO3 are called carbonate apatite.

Which of the following abnormal crystals is often associated with formation of renal calculi?

Cystine

Cystinuria is caused by an autosomal recessive defect in the tubular reabsorption of dibasic amino acids (a renal-type aminoaciduria). Cystine crystals are highly insoluble and form kidney stones. Tyrosine crystals form fine dark sheaves or needles and may result from liver disease or tyrosinosis, an overflow aminoaciduria. Leucine crystals form yellow spheres with concentric rings and are seen in chronic liver disease. Ampicillin (rarely) forms long colorless prisms in sheaves in some patients being treated with high doses.

Which statement about renal calculi is true?

Calcium oxalate and calcium phosphate account for about three-fourths of all stones

Three-fourths of all stones contain calcium and three-fourths of these contain calcium oxalate. Stones are usually composed of several inorganic salts, but calcium oxalate is the most common component of urinary stones. Oxalates are hard, dark, and coarse stones. Uric acid stones are always pigmented yellow to reddish brown. They are small translucent stones not apparent on x-ray. Stones made of primarily calcium phosphate (as hydroxyapatite) are light and crumble easily. Stones made of struvite (ammonium magnesium phosphate) are radiodense and lodge in the renal pelvis, forming an outline of the structures resembling the antlers of a deer (staghorn calculi).